Diagnosis and treatment of infectious vaginitis: Proposal for a new algorithm.

Background: Vaginitis is the most common gynecologic diagnosis in primary care, and most women have at least one episode during their lives. The need for standardized strategies to diagnose and treat vaginitis, both in primary care and among gynecologists, is emphasized. The Brazilian Group for Vaginal Infections (GBIV, acronym in Portuguese) aimed to update the practical approach to affected women by reviewing and discussing recent literature, and developing algorithms for diagnosis and treatment of vaginitis. Methods: A literature search within biomedical databases PubMed and SCieLo was conducted in January 2022. The available literature was evaluated by three experienced researchers, members of the GBIV, to summarize the main data and develop practical algorithms. Results and conclusion: Detailed algorithms were developed with the main goal to improve gynecological practice considering different scenarios and access to diagnostic tools, from the simplest to the most complex tests. Different age groups and specific contexts were also considered. The combination of anamnesis, gynecological examination, and complementary tests remains the basis of a proper diagnostic and therapeutic approach. Periodic updates of these algorithms are warranted as new evidence becomes available.

HELLP syndrome and COVID-19: A minor revision of a possible new "COVID-19-linked HELLP-like syndrome".

To report the characteristics described in the literature on a possible new "COVID-19-linked HELLP-like syndrome" in pregnant women with COVID-19: its association with the severity; prevalence; clinical; laboratory; pathophysiological and therapeutic management differences from the classic HELLP syndrome and their impact on outcomes. Observational, cohort, case-control, case-series and case-report studies were included. Data were extracted independently by the authors of the study, to ensure accuracy, consistency and performed the quality assessment. The database search resulted in 77 references, of which two satisfied the eligibility criteria. In these 2 studies we found a possible "COVID-19-linked HELLP-like syndrome", associated with severe COVID-19. There is a high possibility of the existence of "COVID-19-linked HELLP-like syndrome" and its association with severe COVID-19 in pregnant women, with a prevalence of 28,6%. Some characteristics of "COVID-19-linked HELLP-like syndrome" and the classic HELLP syndrome are similar. Differential diagnosis indicated two different types of therapeutic management: conservative for "COVID-19-linked HELLP-like syndrome" and delivery for the HELLP syndrome. HELLP clinical management is mandatory for both.

Recurrence in Cervical High-Grade Squamous Intraepithelial Lesion: The Role of the Excised Endocervical Canal Length-Analysis of 2,427 Patients.

OBJECTIVE: This study aimed to evaluate the influence of the excised canal length on relapse rates of cervical high-grade squamous intraepithelial lesion (HSIL) treated by loop electrosurgical excision procedure and to find a cut-off point, above which lower recurrence rates could be observed, with low probability of compromising future obstetric outcome, and the relationship with other individual factors related to HSIL recurrence. METHOD: This was a retrospective cohort study of 2,427 women diagnosed with cervical intraepithelial neoplasia CIN2+ who underwent cervical conization using the high-frequency loop electrosurgical excision procedure surgery technique, to analyze the role of endocervical canal length associated with individual factors in the recurrent disease after CIN2+ treatment and determine a cut-off point for the excised canal length needed to decrease the risk of disease relapse. RESULTS: In 2,427 cases, the relapse rate of HSIL treated was 12%. Compromised margins of conization, HIV+, and endocervical canal length were related directly to relapses ( p < .001). The cut-off point, by receiver operating characteristic curve, to calculate the endocervical canal length related to relapses was 1.25 cm of canal excised. Canal length of less than 1.25 cm increased the recurrence rate 2.5 times. Compromised margins and HIV+ increased recurrence rates by more than 5 times. CONCLUSION: Cervical HSIL recurrence was directly related to the endocervical canal length: excised canal length of 1.25 cm or more decreases recurrence rate; HIV and compromised margins increase the chance of recurrence by more than 5 times.

Vaginal Microbiome Components as Correlates of Cervical Human Papillomavirus Infection.

BACKGROUND: Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota. METHODS: We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3-V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants' sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI). RESULTS: Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517-.8527) for MB score and 0.7027 (95% CI, .6419-.7636) for SBC score (P = .0163). CONCLUSIONS: The proposed MB score is strongly correlated with hrHPV positivity-exceeding the predictive value of behavioral variables-suggesting its potential as an indicator of infection and possible value for clinical risk stratification.

Inside the pocket: Critical elements of HLA-mediated susceptibility to cervical precancerous lesions.

Human papillomavirus (HPV) infection is a necessary cause for cervical cancer (CC), but it also depends on genetic factors, such as HLA polymorphism. However, few reports addressed the role of amino acids residues at the HLA peptide-binding cleft in HPV-related cervical disease. Therefore, we aimed to investigate the association between HLA-B, HLA-C, and HLA-DRB1 polymorphism and amino acid residues composing the pockets of the peptide-binding cleft of the respective polypeptide chains with cervical intraepithelial neoplasia (CIN II/III). HLA typing was performed by PCR-SSOP in 184 women with CIN II/III and 174 controls from South Brazil. Associations were estimated by multivariate logistic regression. FDR test was performed to correct the p-value for multiple comparisons. HLA-DRB1*13:01 was associated with protection against CIN II/III, while HLA-C*03:04 was associated with susceptibility. The amino acid residues isoleucine, tyrosine, and leucine at positions 95, 116, and 163 of HLA-C, respectively, were associated with CIN II/III susceptibility. In contrast, serine at positions 11 and 13 of HLA-DRB1 was associated with protection against the disease. Our results confirm previously reported associations between HLA and cervical diseases caused by HPV and suggest a role for amino acid residues at different positions of HLA-C and HLA-DRB1 in CIN II/III. This finding may be further explored to better understand the genetic risk and the influence of immune response to CC development.

Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features.

Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described. Objective: To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group). Method: The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker. Results: Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis. Conclusion: Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.

SARS-CoV-2 in asymptomatic pregnant women in South Brazil: RT-PCR and serological detection.

OBJECTIVES: This study aims to detect the SARS-CoV-2 infection prevalence in asymptomatic pregnant women. METHODS: A group of 195 asymptomatic pregnant women who attended the prenatal care outclinic and to the obstetric emergency department was tested concomitantly for SARS-CoV-2 by RT-PCR and serological tests. RESULTS: The virus was detected by RT-PCR in two (1.02%) cases and 17 (8.71%) patients had antibodies detected by immunochromatographic tests. CONCLUSIONS: Due to the high risk of this emerging infection in the health of pregnant women, fetuses and newborns, we suggest the universal screening of all pregnant women admitted to hospital through the combined method RT-PCR and serological.

MICA and KLRK1 genes and their impact in cervical intraepithelial neoplasia development in the southern Brazilian population.

Cervical carcinoma and cervical intraepithelial neoplasia (CIN) are associated with persistent infection by oncogenic subtypes of HPV (Human Papillomavirus). Factors linked to immunity, genetics and others like oral contraceptive use, sexual behavior, coinfections with other microorganisms and smoking seem to influence the mechanisms that determine regression or progression to CIN and cervical cancer. We investigated the effect of the MHC class I chain-related gene A (MICA) and Killer Cell Lectin Like receptor K1 (KLRK1) genes on cervical cancer and CIN lesions susceptibility in a group of 195 patients from southern Brazil. There were found a significantly higher number of ex-smokers in the control group (p = 0.005). There were more oral contraceptives (OC) users in the patient group. MICA*008:01/04 allele showed a significant difference between patient and control groups (p = 0.03; OR = 0.63, 95% CI 0.41-0.96), as well as MICA*018:01(p = 0.004, OR = 0.15, 95% CI 0.03-0.64) and MICA*002:01/020 (p = 0.01; OR = 0.60, 95% CI 0.40-0.88). We also analyzed cases and controls according to the MICA-129 genotypes (Met/Val). There was found a difference (p = 0.02) with the Met/Val genotype in a higher frequency in controls and Val/Val and Val/MICA del at a higher frequency in the patient group. For the KLRK1 gene there was no significant difference between groups.

Mycoplasma genitalium, a stealth female reproductive tract.

Mycoplasma genitalium was first isolated from the urethral swabs of two symptomatic men with urethritis in 1980. It is a sexually transmitted bacterium associated with a number of urogenital conditions in women like cervicitis, endometritis, pelvic inflammatory disease, infertility, and susceptibility to human immunodeficiency virus (HIV). However, M. genitalium may also act like a stealth pathogen at female reproductive tract, giving no symptoms. Its prevalence varies between different groups, with the average being 0.5-10% in the general population and 20-40% in women with sexually transmitted infections. The recommended treatment of this infection is azithromycin as a single 1-g dose. However, in recent years, macrolide resistance has increased which is significantly lowering the cure rate, being less than 50% in some studies. New treatment regimens need to be investigated due to increasing drug resistance. The discussion and suggestion of an algorithm for management of this infection is the highlight of this paper.

Is there a role played by HLA-E, if any, in HPV immune evasion?

Cervical cancer incidence worldwide exceeds half a million new cases per year. The human papillomavirus (HPV) being the major causative agent of CC uses a variety of strategies to evade immune surveillance, where the immune status varies amongst individuals. This immune evasion altered by HPV is reflected in persistent infections, causing the evolution of cervical neoplasia. The role of the immune system in viral recognition and elimination is of extreme relevance in the development of CC. The interactions of the HLA-E ligand in the target cell along with CD94/NKG2 receptors, which are expressed predominantly, but not exclusively, on NK cells' surface, are responsible for activating or inhibiting cytotoxic activity according to their function. The engagement between HLA-E and CD94/NKG2 molecules is one of the fundamental surveillance mechanisms in patients with CIN I, II and III, where HLA-E expression increases significantly, especially in HPV 16 and 18 infections. Higher HLA-E expression was observed in most histopathological types of CC, and at the same time was correlated to best survival of the patient. This review aims to summarize and discuss the immunological role of HLA-E in the context of HPV infection and immune system evasion, and the oncogenic process of cervical cancer.

Determinants of Acquisition and Clearance of Human Papillomavirus Infection in Previously Unexposed Young Women.

BACKGROUND: Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV. METHODS: Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000-September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time. RESULTS: On short-term follow-up (0-27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64-34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37-3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19-3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0-76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08-1.78) and black women (RR, 1.64; 95% CI, 1.04-2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43-0.98). CONCLUSIONS: We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

MASP-1 and MASP-2 Serum Levels Are Associated With Worse Prognostic in Cervical Cancer Progression.

Background: MBL-associated serine proteases (MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19) are key factors in the activation of the lectin pathway of complement. Serum levels of these components have been associated with recurrence and poor survival of some types of cancer, such as colorectal and ovarian cancer. In this investigation, we determined the serum levels of MASP-1, MASP-2, MASP-3, MAp-44, and MAp-19 in patients with cervical cancer and cervical intraepithelial neoplasia (CIN). Methods:A total of 351 women who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital in Curitiba-Brazil, were enrolled in the study. Based on their latest cervical colposcopy-guided biopsy results, they were divided into four groups: CIN-I: n = 52; CIN-II: n = 73; CIN-III: n = 141; and invasive cancer: n = 78. All the serum protein levels were determined by time-resolved immunofluorometric assay (TRIFMA). Results:Patients with invasive cancer presented significantly higher MASP-2, MASP-1, and MAp-19 serum levels than other groups (p < 0.0001; p = 0.012; p = 0.025 respectively). No statistically significant differences in MASP-3 and MAp-44 serum levels were found between the four studied groups. In addition, high MASP-2, MASP-1, and MAp-19 serum levels were significantly associated with poor survival in patients with invasive cancer and relapse (p = 0.002, p = 0.0035 and p = 0.025, respectively). Conclusion:High MASP-2, MASP-1, and MAp-19 serum levels were associated with cervical cancer progression and worse disease prognosis. These novel findings demonstrate the involvement of the serine proteases of the lectin pathway in the pathogenesis of cervical cancer and future investigations should clarify their role in the disease process.

Methylation in host and viral genes as marker of aggressiveness in cervical lesions: Analysis in 543 unscreened women.

OBJECTIVE: The present study aimed to evaluate the association between altered methylation and histologically confirmed high grade cervical intraepithelial neoplasia (hgCIN). METHODS: Methylation levels in selected host (CADM1, MAL, DAPK1) and HPV (L1_I, L1_II, L2) genes were measured by pyrosequencing in DNA samples obtained from 543 women recruited in Curitiba (Brazil), 249 with hgCIN and 294 without cervical lesions. Association of methylation status with hgCIN was estimated by Odds Ratio (OR) with 95% confidence interval (CI). RESULTS: The mean methylation level increased with severity of the lesion in the host and viral genes (p-trend < 0.05), with the exception of L1_II region (p-trend = 0.075). Positive association was found between methylation levels for host genes and CIN2 and CIN3 lesions respectively [CADM1: OR 4.17 (95%CI 2.03-8.56) and OR 9.54 (95%CI 4.80-18.97); MAL: OR 5.98 (95%CI 2.26-15.78) and OR 22.66 (95%CI 9.21-55.76); DAPK1: OR 3.37 (95%CI 0.93-12.13) and OR 6.74 (95%CI 1.92-23.64)]. Stronger risk estimates were found for viral genes [L1_I: OR 10.74 (95%CI 2.66-43.31) and OR 15.00 (95%CI 3.00-74.98); L1_II: OR 73.18 (95%CI 4.07-1315.94) and OR 32.50 (95%CI 3.86-273.65); L2: OR 4.73 (95%CI 1.55-14.44) and OR 10.62 (95%CI 2.60-43.39)]. The cumulative effect of the increasing number of host and viral methylated genes was associated with the risk of CIN2 and CIN3 lesions (p-trend < 0.001). CONCLUSIONS: Our results, empowered by a wide cervical sample series with a large number of hgCIN, supported the role of methylation as marker of aggressiveness.

MICA-129 A/G dimorphism, its relation to soluble mica plasma level and spontaneous preterm birth: A case-control study.

The aim of this case- control study was to investigate the association between preterm birth (PTB), MICA-129 A/G dimorphism and sMICA levels. Fifty pregnant women with singleton pregnancy and previous PTB, or clinic diagnostic of threatened preterm labor in the actual pregnancy, or cervical length less than 25 mm and 50 healthy pregnant women were enrolled. DNA was extracted for genotyping for MICA-129 A/G by real-time PCR and sMICA plasma level was quantified by sandwich ELISA assay. Clinical and socioeconomic characteristics, results of TaqMan® genotyping and ELISA quantification were compared between the groups using qui-square, Fisher´s exact or Mann-Whitney test. A binary logistic regression model was used to predict PTB. The correlation between MICA-129 A/G genotypes and sMICA levels was investigated. There were not statistically significant differences between MICA-129 A/G polymorphism and sMICA plasma level.There was found a correlation between MICA-129 val/val genotype and higher levels of sMICA (ρ: -0.342; p:0.001). The presence of MICA-129  val/val genotype may be influencing sMICA expression.

Women infected with HIV and the impact of associated sexually transmitted infections.

OBJECTIVE: To review the relationship between concomitant sexually transmitted infections in women infected with HIV. METHODS: PubMed and Scopus were searched for articles published in English and Portuguese between January 1, 1994, and December 31, 2015, using relevant keywords, including AIDS, HIV, female genital diseases, and sexually transmitted infections. Articles that associated sexually transmitted infections with HIV-infected women were selected for inclusion. Those that only investigated prevalence in pregnant women or focused on social or behavioral aspects were excluded. RESULTS: Of 108 identified articles, 24 were included. When correlated with HIV, genital herpes demonstrated an increased recurrence rate and increased replication rate for HIV in the mucosa. In HIV-positive women, syphilis can cause more genital ulcers. Bacterial vaginosis provides a pool of microorganisms that can increase the viral copy levels of genital HIV. Chlamydia, gonorrhea, and candidiasis may be more severe and complicated in women infected with HIV. CONCLUSIONS: Screening of HIV-positive patients who could have other sexually transmitted infections is important to protect women and decrease the risk of transmission.

Mannose-Binding Lectin Does Not Act as a Biomarker for the Progression of Preinvasive Lesions of Invasive Cervical Cancer.

OBJECTIVE: To evaluate serum concentrations of mannose-binding lectin (MBL) in women presenting with different human papillomavirus (HPV)-associated cervical lesions. SUBJECTS AND METHODS: A total of 364 women, who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital (HEG), Curitiba, Brazil, were enrolled in the study. Based on the latest cervical colposcopy-guided biopsy results, the women were divided into 4 groups: cervical intraepithelial neoplasia CIN-I (n = 54), CIN-II (n = 72), CIN-III (n = 145), and invasive cancer (n = 93). A time-resolved immunofluorometric assay was used to measure the MBL concentrations in serum. The statistical analysis was done using GraphPad Prism 6.0. Comparisons were performed by Kruskal-Wallis and Mann-Whitney tests and analyzed by χ2 test; continuous variables are presented as medians and categorical variables as frequencies. RESULTS: The median MBL concentrations in decreasing order were as follows: invasive cancer: 1,452 ng/mL, CIN-I: 1,324 ng/mL, CIN-II: 1,104 ng/mL, and CIN-III 1,098 ng/mL. However, no statistical significance was found among the 4 groups with HPV-associated lesions (p = 0.11). Equally, the MBL levels did not show a significant association between the age of the patients and the severity of the cervical lesions (p = 0.68). No statistical significance was found in the median values of MBL or in the status of MBL deficient (<100 ng/mL) and high producers (>1,000 ng/mL) among the women in each group (p = 0.77). CONCLUSION: In this study, there was no statistically significant difference in MBL serum levels among the groups with CIN. Hence MBL serum concentration appeared not to have influenced the progression of HPV-related preinvasive cervical lesions into invasive cancer.

Evaluation of Type Replacement Following HPV16/18 Vaccination: Pooled Analysis of Two Randomized Trials.

Background: Current HPV vaccines do not protect against all oncogenic HPV types. Following vaccination, type replacement may occur, especially if different HPV types competitively interact during natural infection. Because of their common route of transmission, it is difficult to assess type interactions in observational studies. Our aim was to evaluate type replacement in the setting of HPV vaccine randomized controlled trials (RCTs). Methods: Data were pooled from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT001226810)-two large-scale, double-blind RCTs of the HPV-16/18 AS04-adjuvanted vaccine-to compare cumulative incidence of nonprotected HPV infections across trial arms after four years. Negative rate difference estimates (rate in control minus vaccine arm) were interpreted as evidence of replacement if the associated 95% confidence interval excluded zero. All statistical tests were two-sided. Results: After applying relevant exclusion criteria, 21 596 women were included in our analysis (HPV arm = 10 750; control arm = 10 846). Incidence rates (per 1000 infection-years) were lower in the HPV arm than in the control arm for grouped nonprotected oncogenic types (rate difference = 1.6, 95% confidence interval [CI] = 0.9 to 2.3) and oncogenic/nononcogenic types (rate difference = 0.2, 95% CI = -0.3 to 0.7). Focusing on individual HPV types separately, no deleterious effect was observed. In contrast, a statistically significant protective effect (positive rate difference and 95% CI excluded zero) was observed against oncogenic HPV types 35, 52, 58, and 68/73, as well as nononcogenic types 6 and 70. Conclusion: HPV type replacement does not occur among vaccinated individuals within four years and is unlikely to occur in vaccinated populations.

Zika virus and pregnancy: An overview.

In May 2015, the first episodes of Zika virus infection of the Latin America were confirmed in Brazil, where currently 196 976 cases were reported. The main route of transmission occurs by Aedes mosquitoes, and the most common symptoms are maculopapular rash, fever, conjunctivitis, polyarthralgia, and periarticular edema. However, the infection is asymptomatic in 80% of the cases. The congenital infection is characterized when the transmission to the fetus occurs during pregnancy, but the mechanisms of how the virus infects the placenta remain unclear. Anatomopathological findings were described in first- and third-trimester human placentas; however, the major affected tissue of the baby is the neural. Several clinical situations were listed in these fetuses, such as neurological, ophthalmological, auditory, and articular alterations. The World Health Organization proposed a new congenital syndrome caused by Zika virus. The virus has an important neurotropism and the main manifestation observed in the syndrome is microcephaly, which is usually severe and associated with other neurological injuries. The appearance of sudden rash in pregnant women determines immediate investigation through RT-PCR and serological analysis. Moreover, the prevention consists in using repellents and avoiding endemic areas, considering that the vaccine is still under development.

Baby born too soon: an overview and the impact beyond the infection.

Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, immunological factors also appear to be involved. Recently, molecular genetic studies have helped us better understand the underlying pathophysiologic processes. During mammalian pregnancy, maternal-fetal tolerance involves a number of immunosuppressive factors produced by placenta. Recently, placenta-derived exosomes have emerged as new immune regulators in the maternal immune tolerance. This review focuses on the specific immune parameters that become altered during human pregnancy, the identity and function of some immune modulators that have been best characterized to date, as well as a comprehensive evaluation of the pregnancy-associated mechanisms that downregulate proinflammatory immunity to a level sufficient to prevent the triggering of premature common pathway of labor and damage to developing organs.